Effect of a 24-week resistance exercise intervention on cognitive function in cognitively normal older adults: The AGUEDA Randomized Controlled Trial

Abstract Objective The AGUEDA trial examined the effects of a 24-week resistance exercise (RE) intervention on executive function (EF) and other cognitive domains in cognitively normal older adults. Method Ninety participants (71.75 ± 3.96 years, 57.8% female) were randomized to an RE group (n = 46) or a control group (n = 44). The RE group performed 180 minutes/week of supervised training, while the control group maintained usual activities. EF and other cognitive domains (e.g., attentional/inhibitory control, episodic memory, processing speed, visuospatial processing, and working memory) were assessed at baseline, and 24 weeks. Intervention effects were analyzed using intention-to-treat (ITT) and per-protocol (PP) approaches, with exploratory subgroup analyses based on sociodemographic and AD-related characteristics. Results EF composite score improved in both groups, with no significant between-group differences (standardized mean difference (SMD) = 0.13, p = 0.37). In addition, the RE group showed significant improvements in attentional/inhibitory control compared to the control group (SMD = 0.43, p < 0.001), while the rest of cognitive domains showed no significant differences (p > 0.05). Subgroup analyses revealed greater EF benefits for the oldest adults, those with lower educational levels, and individuals with higher subjective cognitive decline (SCD) at baseline. RE had an effect on knee extension strength (SMD = 0.25, p = 0.02), which was positively correlated with better EF (r = 0.38, p = 0.0005) and improved episodic memory (r = 0.31, p = 0.008). Conclusion The 24-week AGUEDA intervention revealed no significant differences in EF or other cognitive domains after 24 weeks. However, participants in the RE group demonstrated significantly greater improvements in attentional/inhibitory control compared to the control group. Moreover, our findings support the notion that RE can yield greater benefits in the more vulnerable subgroups, such as the oldest participants, those with SCD or fewer years of education. Although the mediation analysis did not find significant indirect effects, lower body muscular strength improvements were positively correlated with better EF and episodic memory, highlighting the potential role of strength in cognitive health.